Clues to the mechanism of cholesterol transfer from the structure of NPC1 middle lumenal domain bound to NPC2

Li, Xiaochun; Saha, Piyali; Li, Jian; Blobel, Günter; Pfeffer, Suzanne R.

doi:10.1073/pnas.1611956113

Clues to the mechanism of cholesterol transfer from the structure of NPC1 middle lumenal domain bound to NPC2

Journal Article · Mon Aug 22 00:00:00 EDT 2016 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1611956113· OSTI ID:1330262

Li, Xiaochun ^[1]; Saha, Piyali ^[2]; Li, Jian ^[2]; Blobel, Günter ^[1]; Pfeffer, Suzanne R. ^[2]

Rockefeller Univ., New York, NY (United States)
Stanford Univ. School of Medicine, Stanford, CA (United States)

Export of LDL-derived cholesterol from lysosomes requires the cooperation of the integral membrane protein Niemann–Pick C1 (NPC1) and a soluble protein, Niemann–Pick C2 (NPC2). Mutations in the genes encoding these proteins lead to Niemann–Pick disease type C (NPC). NPC2 binds to NPC1’s second (middle), lumenally oriented domain (MLD) and transfers cholesterol to NPC1’s N-terminal domain (NTD). Here, we report the 2.4-Å resolution crystal structure of a complex of human NPC1–MLD and NPC2 bearing bound cholesterol-3-O-sulfate. NPC1–MLD uses two protruding loops to bind NPC2, analogous to its interaction with the primed Ebola virus glycoprotein. Here, docking of the NPC1–NPC2 complex onto the full-length NPC1 structure reveals a direct cholesterol transfer tunnel between NPC2 and NTD cholesterol binding pockets, supporting the “hydrophobic hand-off” cholesterol transfer model.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: American Diabetes Association; Ara Parseghian Medical Research Fund; Howard Hughes Medical Inst; National Inst. of Diabetes and Digestive and Kidney Diseases; National Inst. of Health

OSTI ID:: 1330262

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 36 Vol. 113; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (37)

Structure of glycosylated NPC 1 luminal domain C reveals insights into NPC 2 and Ebola virus interactions Zhao, Yuguang; Ren, Jingshan; Harlos, Karl FEBS Letters, Vol. 590, Issue 5 https://doi.org/10.1002/1873-3468.12089	journal	February 2016
NMRPipe: A multidimensional spectral processing system based on UNIX pipes Delaglio, Frank; Grzesiek, Stephan; Vuister, GeertenW. Journal of Biomolecular NMR, Vol. 6, Issue 3 https://doi.org/10.1007/BF00197809	journal	November 1995
Exploring the gas access routes in a [NiFeSe] hydrogenase using crystals pressurized with krypton and oxygen Zacarias, Sónia; Temporão, Adriana; Carpentier, Philippe JBIC Journal of Biological Inorganic Chemistry, Vol. 25, Issue 6 https://doi.org/10.1007/s00775-020-01814-y	journal	August 2020
Ebola Virus Entry into Host Cells: Identifying Therapeutic Strategies Rhein, Bethany A.; Maury, Wendy J. Current Clinical Microbiology Reports, Vol. 2, Issue 3 https://doi.org/10.1007/s40588-015-0021-3	journal	July 2015
Role of lysosomal acid lipase in the metabolism of plasma low density lipoprotein. Observations in cultured fibroblasts from a patient with cholesteryl ester storage disease. Goldstein, Jl; Dana, Se; Faust, Jr Journal of Biological Chemistry, Vol. 250, Issue 21 https://doi.org/10.1016/S0021-9258(19)40786-2	journal	November 1975
Mechanism of Cholesterol Transfer from the Niemann-Pick Type C2 Protein to Model Membranes Supports a Role in Lysosomal Cholesterol Transport Cheruku, Sunita R.; Xu, Zhi; Dutia, Roxanne Journal of Biological Chemistry, Vol. 281, Issue 42 https://doi.org/10.1016/S0021-9258(19)84073-5	journal	October 2006
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
The sterol-sensing domain: multiple families, a unique role? Kuwabara, Patricia E.; Labouesse, Michel Trends in Genetics, Vol. 18, Issue 4 https://doi.org/10.1016/S0168-9525(02)02640-9	journal	April 2002
Protein Sensors for Membrane Sterols Goldstein, Joseph L.; DeBose-Boyd, Russell A.; Brown, Michael S. Cell, Vol. 124, Issue 1 https://doi.org/10.1016/j.cell.2005.12.022	journal	January 2006
Structure of N-Terminal Domain of NPC1 Reveals Distinct Subdomains for Binding and Transfer of Cholesterol Kwon, Hyock Joo; Abi-Mosleh, Lina; Wang, Michael L. Cell, Vol. 137, Issue 7 https://doi.org/10.1016/j.cell.2009.03.049	journal	June 2009
Ebola Viral Glycoprotein Bound to Its Endosomal Receptor Niemann-Pick C1 Wang, Han; Shi, Yi; Song, Jian Cell, Vol. 164, Issue 1-2 https://doi.org/10.1016/j.cell.2015.12.044	journal	January 2016
Structural Insights into the Niemann-Pick C1 (NPC1)-Mediated Cholesterol Transfer and Ebola Infection Gong, Xin; Qian, Hongwu; Zhou, Xinhui Cell, Vol. 165, Issue 6 https://doi.org/10.1016/j.cell.2016.05.022	journal	June 2016
Identification of Surface Residues on Niemann-Pick C2 Essential for Hydrophobic Handoff of Cholesterol to NPC1 in Lysosomes Wang, Michael L.; Motamed, Massoud; Infante, Rodney E. Cell Metabolism, Vol. 12, Issue 2 https://doi.org/10.1016/j.cmet.2010.05.016	journal	August 2010
Mechanism of Cholesterol Transfer from the Niemann-Pick Type C2 Protein to Model Membranes Supports a Role in Lysosomal Cholesterol Transport Cheruku, Sunita R.; Xu, Zhi; Dutia, Roxanne Journal of Biological Chemistry, Vol. 281, Issue 42 https://doi.org/10.1016/s0021-9258(19)84073-5	journal	October 2006
Computational Studies of the Cholesterol Transport between NPC2 and the N-Terminal Domain of NPC1 (NPC1(NTD)) Estiu, Guillermina; Khatri, Nazir; Wiest, Olaf Biochemistry, Vol. 52, Issue 39 https://doi.org/10.1021/bi4005478	journal	September 2013
Ebola virus entry requires the host-programmed recognition of an intracellular receptor: Niemann-Pick C1 is a critical filovirus receptor Miller, Emily Happy; Obernosterer, Gregor; Raaben, Matthijs The EMBO Journal, Vol. 31, Issue 8 https://doi.org/10.1038/emboj.2012.53	journal	March 2012
Ebola virus entry requires the cholesterol transporter Niemann–Pick C1 Carette, Jan E.; Raaben, Matthijs; Wong, Anthony C. Nature, Vol. 477, Issue 7364 https://doi.org/10.1038/nature10348	journal	August 2011
Small molecule inhibitors reveal Niemann–Pick C1 is essential for Ebola virus infection Côté, Marceline; Misasi, John; Ren, Tao Nature, Vol. 477, Issue 7364 https://doi.org/10.1038/nature10380	journal	August 2011
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation Tillu, Vikas A.; Rae, James; Gao, Ya Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-21035-4	journal	February 2021
Multi-functionality of a tryptophan residue conserved in substrate-binding groove of GH19 chitinases Nagata, Takuya; Shinya, Shoko; Ohnuma, Takayuki Scientific Reports, Vol. 11, Issue 1 https://doi.org/10.1038/s41598-021-81903-3	journal	January 2021
NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes Infante, Rodney E.; Wang, Michael L.; Radhakrishnan, Arun Proceedings of the National Academy of Sciences, Vol. 105, Issue 40 https://doi.org/10.1073/pnas.0807328105	journal	September 2008
Niemann-Pick type C 1 function requires lumenal domain residues that mediate cholesterol-dependent NPC2 binding Deffieu, M. S.; Pfeffer, S. R. Proceedings of the National Academy of Sciences, Vol. 108, Issue 47 https://doi.org/10.1073/pnas.1110439108	journal	November 2011
Glycosylation inhibition reduces cholesterol accumulation in NPC1 protein-deficient cells Li, Jian; Deffieu, Maika S.; Lee, Peter L. Proceedings of the National Academy of Sciences, Vol. 112, Issue 48 https://doi.org/10.1073/pnas.1520490112	journal	November 2015
Structure of human Niemann–Pick C1 protein Li, Xiaochun; Wang, Jiawei; Coutavas, Elias Proceedings of the National Academy of Sciences, Vol. 113, Issue 29 https://doi.org/10.1073/pnas.1607795113	journal	June 2016
Multiple Surface Regions on the Niemann-Pick C2 Protein Facilitate Intracellular Cholesterol Transport McCauliff, Leslie A.; Xu, Zhi; Li, Ran Journal of Biological Chemistry, Vol. 290, Issue 45 https://doi.org/10.1074/jbc.M115.667469	journal	August 2015
Mechanism of Cholesterol Transfer from the Niemann-Pick Type C2 Protein to Model Membranes Supports a Role in Lysosomal Cholesterol Transport Cheruku, Sunita R.; Xu, Zhi; Dutia, Roxanne Journal of Biological Chemistry, Vol. 281, Issue 42 https://doi.org/10.1074/jbc.M602765200	journal	April 2006
Structural Basis of Sterol Binding by NPC2, a Lysosomal Protein Deficient in Niemann-Pick Type C2 Disease Xu, Sujuan; Benoff, Brian; Liou, Heng-Ling Journal of Biological Chemistry, Vol. 282, Issue 32 https://doi.org/10.1074/jbc.M703848200	journal	June 2007
Purified NPC1 Protein: I. BINDING OF CHOLESTEROL AND OXYSTEROLS TO A 1278-AMINO ACID MEMBRANE PROTEIN Infante, Rodney E.; Abi-Mosleh, Lina; Radhakrishnan, Arun Journal of Biological Chemistry, Vol. 283, Issue 2 https://doi.org/10.1074/jbc.M707943200	journal	November 2007
Purified NPC1 Protein: II. LOCALIZATION OF STEROL BINDING TO A 240-AMINO ACID SOLUBLE LUMINAL LOOP Infante, Rodney E.; Radhakrishnan, Arun; Abi-Mosleh, Lina Journal of Biological Chemistry, Vol. 283, Issue 2 https://doi.org/10.1074/jbc.M707944200	journal	November 2007
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Niemann-Pick type C disease: molecular mechanisms and potential therapeutic approaches: Therapeutics for NPC disease Rosenbaum, Anton I.; Maxfield, Frederick R. Journal of Neurochemistry, Vol. 116, Issue 5 https://doi.org/10.1111/j.1471-4159.2010.06976.x	journal	January 2011
A receptor-mediated pathway for cholesterol homeostasis Brown, Ms; Goldstein, Jl Science, Vol. 232, Issue 4746 https://doi.org/10.1126/science.3513311	journal	April 1986
PHENIX: a comprehensive Python-based system for macromolecular structure solution. Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.45787	text	January 2010
Identification of NPC1 as the target of U18666A, an inhibitor of lysosomal cholesterol export and Ebola infection Lu, Feiran; Liang, Qiren; Abi-Mosleh, Lina eLife, Vol. 4 https://doi.org/10.7554/eLife.12177	journal	December 2015
Protein flexibility is required for vesicle tethering at the Golgi Cheung, Pak-yan Patricia; Limouse, Charles; Mabuchi, Hideo eLife, Vol. 4 https://doi.org/10.7554/eLife.12790	journal	December 2015

Cited By (39)

Niemann-Pick Type C Disease Reveals a Link between Lysosomal Cholesterol and PtdIns(4,5)P2 That Regulates Neuronal Excitability Vivas, Oscar; Tiscione, Scott A.; Dixon, Rose E. Cell Reports, Vol. 27, Issue 9 https://doi.org/10.1016/j.celrep.2019.04.099	journal	May 2019
Quantitating the epigenetic transformation contributing to cholesterol homeostasis using Gaussian process Wang, Chao; Scott, Samantha M.; Subramanian, Kanagaraj Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-12969-x	journal	November 2019
Structural basis for itraconazole-mediated NPC1 inhibition Long, Tao; Qi, Xiaofeng; Hassan, Abdirahman Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-019-13917-5	journal	January 2020
Author Correction: Naturally-occurring cholesterol analogues in lipid nanoparticles induce polymorphic shape and enhance intracellular delivery of mRNA Patel, Siddharth; Ashwanikumar, N.; Robinson, Ema Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-020-17025-7	journal	July 2020
Large-scale computational drug repositioning to find treatments for rare diseases Govindaraj, Rajiv Gandhi; Naderi, Misagh; Singha, Manali npj Systems Biology and Applications, Vol. 4, Issue 1 https://doi.org/10.1038/s41540-018-0050-7	journal	March 2018
Crystal structure of the DNA-binding domain of Myelin-gene Regulatory Factor Zhen, Xiangkai; Li, Bowen; Hu, Fen Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/s41598-017-03768-9	journal	June 2017
Characterization of cholesterol homeostasis in sphingosine-1-phosphate lyase-deficient fibroblasts reveals a Niemann-Pick disease type C-like phenotype with enhanced lysosomal Ca2+ storage Vienken, Hans; Mabrouki, Nathalie; Grabau, Katja Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/srep43575	journal	March 2017
Recent neuroimaging, neurophysiological, and neuropathological advances for the understanding of NPC Benussi, Alberto; Cotelli, Maria Sofia; Padovani, Alessandro F1000Research, Vol. 7 https://doi.org/10.12688/f1000research.12361.1	journal	January 2018
Pathogenic mycobacteria achieve cellular persistence by inhibiting the Niemann-Pick Type C disease cellular pathway Fineran, Paul; Lloyd-Evans, Emyr; Lack, Nathan A. Wellcome Open Research, Vol. 1 https://doi.org/10.12688/wellcomeopenres.10036.2	journal	January 2016
Mechanisms of action of Coxiella burnetii effectors inferred from host-pathogen protein interactions Wallqvist, Anders; Wang, Hao; Zavaljevski, Nela PLOS ONE, Vol. 12, Issue 11 https://doi.org/10.1371/journal.pone.0188071	journal	November 2017
Structural basis of human ORP1-Rab7 interaction for the late-endosome and lysosome targeting Tong, Junsen; Tan, Lingchen; Chun, ChangJu PLOS ONE, Vol. 14, Issue 2 https://doi.org/10.1371/journal.pone.0211724	journal	February 2019
Exacerbating and reversing lysosomal storage diseases: from yeast to humans Rajakumar, Tamayanthi; Munkacsi, Andrew B.; Sturley, Stephen L. Microbial Cell, Vol. 4, Issue 9 https://doi.org/10.15698/mic2017.09.588	journal	September 2017
Identifying the structure-activity relationship of leelamine necessary for inhibiting intracellular cholesterol transport Gowda, Raghavendra; Inamdar, Gajanan S.; Kuzu, Omer Oncotarget, Vol. 8, Issue 17 https://doi.org/10.18632/oncotarget.16002	journal	March 2017
Niemann-Pick C2 Proteins: A New Function for an Old Family Zhu, Jiao; Guo, Mengbuo; Ban, Liping Frontiers in Physiology, Vol. 9 https://doi.org/10.3389/fphys.2018.00052	journal	January 2018
Simulations of NPC1(NTD):NPC2 Protein Complex Reveal Cholesterol Transfer Pathways Hodošček, Milan; Elghobashi-Meinhardt, Nadia International Journal of Molecular Sciences, Vol. 19, Issue 9 https://doi.org/10.3390/ijms19092623	journal	September 2018
Lipid–Protein Interactions in Niemann–Pick Type C Disease: Insights from Molecular Modeling Wheeler, Simon; Schmid, Ralf; Sillence, Dan J. International Journal of Molecular Sciences, Vol. 20, Issue 3 https://doi.org/10.3390/ijms20030717	journal	February 2019
NPC1 Deficiency in Mice is Associated with Fetal Growth Restriction, Neonatal Lethality and Abnormal Lung Pathology Rodriguez-Gil, Jorge L.; Watkins-Chow, Dawn E.; Baxter, Laura L. Journal of Clinical Medicine, Vol. 9, Issue 1 https://doi.org/10.3390/jcm9010012	journal	December 2019
Odorant-Binding Proteins as Sensing Elements for Odour Monitoring Pelosi, Paolo; Zhu, Jiao; Knoll, Wolfgang Sensors, Vol. 18, Issue 10 https://doi.org/10.3390/s18103248	journal	September 2018
Lysosomal membrane glycoproteins bind cholesterol and contribute to lysosomal cholesterol export Li, Jian; Pfeffer, Suzanne R. eLife, Vol. 5 https://doi.org/10.7554/elife.21635	journal	September 2016
Lysosomal cholesterol export reconstituted from fragments of Niemann-Pick C1 Trinh, Michael Nguyen; Brown, Michael S.; Seemann, Joachim eLife, Vol. 7 https://doi.org/10.7554/elife.38564	journal	July 2018
Intracellular cholesterol trafficking is dependent upon NPC2 interaction with lysobisphosphatidic acid McCauliff, Leslie A.; Langan, Annette; Li, Ran eLife, Vol. 8 https://doi.org/10.7554/elife.50832	journal	October 2019
Comparative study of the effect of disease causing and benign mutations in position Q92 on cholesterol binding by the NPC1 n-terminal domain Petukh, Marharyta; Zhulin, Igor B. Proteins: Structure, Function, and Bioinformatics, Vol. 86, Issue 11 https://doi.org/10.1002/prot.25597	journal	October 2018
From radioactive ligands to biosensors: binding methods with olfactory proteins Pelosi, Paolo; Zhu, Jiao; Knoll, Wolfgang Applied Microbiology and Biotechnology, Vol. 102, Issue 19 https://doi.org/10.1007/s00253-018-9253-5	journal	July 2018
Changes in global gene expression indicate disordered autophagy, apoptosis and inflammatory processes and downregulation of cytoskeletal signalling and neuronal development in patients with Niemann–Pick C disease Hetmańczyk-Sawicka, Katarzyna; Iwanicka-Nowicka, Roksana; Fogtman, Anna neurogenetics, Vol. 21, Issue 2 https://doi.org/10.1007/s10048-019-00600-6	journal	January 2020
Prospective Turkish Cohort Study to Investigate the Frequency of Niemann-Pick Disease Type C Mutations in Consanguineous Families with at Least One Homozygous Family Member Topçu, Meral; Aktas, Dilek; Öztoprak, Merih Molecular Diagnosis & Therapy, Vol. 21, Issue 6 https://doi.org/10.1007/s40291-017-0293-9	journal	August 2017
ER–lysosome contacts enable cholesterol sensing by mTORC1 and drive aberrant growth signalling in Niemann–Pick type C Lim, Chun-Yan; Davis, Oliver B.; Shin, Hijai R. Nature Cell Biology, Vol. 21, Issue 10 https://doi.org/10.1038/s41556-019-0391-5	journal	September 2019
3.3 Å structure of Niemann–Pick C1 protein reveals insights into the function of the C-terminal luminal domain in cholesterol transport Li, Xiaochun; Lu, Feiran; Trinh, Michael N. Proceedings of the National Academy of Sciences, Vol. 114, Issue 34 https://doi.org/10.1073/pnas.1711716114	journal	August 2017
NPC intracellular cholesterol transporter 1 (NPC1)-mediated cholesterol export from lysosomes Pfeffer, Suzanne R. Journal of Biological Chemistry, Vol. 294, Issue 5 https://doi.org/10.1074/jbc.tm118.004165	journal	February 2019
Quantitative Analysis of the Proteome Response to the Histone Deacetylase Inhibitor (HDACi) Vorinostat in Niemann-Pick Type C1 disease Subramanian, Kanagaraj; Rauniyar, Navin; Lavalleé-Adam, Mathieu Molecular & Cellular Proteomics, Vol. 16, Issue 11 https://doi.org/10.1074/mcp.m116.064949	journal	August 2017
Life in the lumen: The multivesicular endosome Gruenberg, Jean Traffic, Vol. 21, Issue 1 https://doi.org/10.1111/tra.12715	journal	October 2019
Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex Qi, Xiaofeng; Schmiege, Philip; Coutavas, Elias Science, Vol. 362, Issue 6410 https://doi.org/10.1126/science.aas8843	journal	August 2018
Cyclodextrin triggers MCOLN1-dependent endo-lysosome secretion in Niemann-Pick type C cells Vacca, Fabrizio; Vossio, Stefania; Mercier, Vincent Journal of Lipid Research, Vol. 60, Issue 4 https://doi.org/10.1194/jlr.m089979	journal	April 2019
Pathogenic mycobacteria achieve cellular persistence by inhibiting the Niemann-Pick Type C disease cellular pathway Fineran, Paul; Lloyd-Evans, Emyr; Lack, Nathan A. Wellcome Open Research, Vol. 1 https://doi.org/10.12688/wellcomeopenres.10036.1	journal	January 2016
The lipid transfer protein Saposin B does not directly bind CD1d for lipid antigen loading Shamin, Maria; Benedyk, Tomasz H.; Graham, Stephen C. Wellcome Open Research, Vol. 4 https://doi.org/10.12688/wellcomeopenres.15368.1	journal	January 2019
The lipid transfer protein Saposin B does not directly bind CD1d for lipid antigen loading Shamin, Maria; Benedyk, Tomasz H.; Graham, Stephen C. Wellcome Open Research, Vol. 4 https://doi.org/10.12688/wellcomeopenres.15368.2	journal	January 2019
Cholesterol binding to the sterol-sensing region of Niemann Pick C1 protein confines dynamics of its N-terminal domain Dubey, Vikas; Bozorg, Behruz; Wüstner, Daniel PLOS Computational Biology, Vol. 16, Issue 10 https://doi.org/10.1371/journal.pcbi.1007554	journal	October 2020
Modeling the efficiency of filovirus entry into cells in vitro: Effects of SNP mutations in the receptor molecule Kim, Kwang Su; Kondoh, Tatsunari; Asai, Yusuke PLOS Computational Biology, Vol. 16, Issue 9 https://doi.org/10.1371/journal.pcbi.1007612	journal	September 2020
A trimeric Rab7 GEF controls NPC1-dependent lysosomal cholesterol export. Van Den Boomen, Dick; Sienkiewicz, Agata; Berlin, Ilana Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.57698	text	January 2020
A trimeric Rab7 GEF controls NPC1-dependent lysosomal cholesterol export Van Den Boomen, Dick J. H.; Sienkiewicz, Agata; Berlin, Ilana Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.59477	text	January 2020

Similar Records

Structure of N-Terminal Domain of NPC1 Reveals Distinct Subdomains for Binding and Transfer of Cholesterol

Journal Article · Mon Sep 20 20:00:00 EDT 2010 · Cell · OSTI ID:1006175

3.3 Å structure of Niemann–Pick C1 protein reveals insights into the function of the C-terminal luminal domain in cholesterol transport

Journal Article · Sun Aug 06 20:00:00 EDT 2017 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1390867

Structure of human Niemann–Pick C1 protein

Journal Article · Tue Jun 14 20:00:00 EDT 2016 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1274750

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Ebola virus glycoprotein
Niemann–Pick type C disease
cholesterol trafficking
crystal structure

Clues to the mechanism of cholesterol transfer from the structure of NPC1 middle lumenal domain bound to NPC2

Citation Formats

References (37)

Cited By (39)

Similar Records

Related Subjects